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Biological heterogeneity in ADNI amnestic mild cognitive impairment

Jasmine Nettiksimmons1, Charles DeCarli2, Susan Landau3

  • 1Department of Psychiatry, University of California-San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|January 15, 2014
PubMed
Abstract

Insights

Mild cognitive impairment (MCI) patients show significant biological differences, impacting Alzheimer's disease (AD) progression. Understanding this heterogeneity is key for predicting clinical outcomes and developing targeted therapies.

Area of Science:

  • Neuroscience
  • Biomarker Research
  • Clinical Neurology

Background:

  • Previous studies of Alzheimer's Disease Neuroimaging Initiative (ADNI) normal controls revealed significant biological heterogeneity.
  • This heterogeneity suggests that individuals with mild cognitive impairment (MCI) may also exhibit diverse biological profiles.

Purpose of the Study:

  • To investigate the biological heterogeneity among ADNI subjects diagnosed with amnestic MCI.
  • To explore the clinical implications of identified subgroups within the MCI population.

Main Methods:

  • Clustering of 138 amnestic MCI subjects from ADNI based on baseline MRI, CSF, and serum biomarkers.
  • Comparison of identified clusters based on longitudinal atrophy rates, cognitive decline trajectories, and time to Alzheimer's disease (AD) conversion.

Main Results:

  • Four distinct clusters emerged, characterized by unique biomarker patterns.
  • Cluster 1 resembled normal controls with low AD conversion rates. Cluster 2 showed early AD pathology markers.
  • Cluster 3 exhibited severe atrophy but near-normal tau, with significant AD conversion. Cluster 4 presented as pre-AD with near-universal conversion.

Conclusions:

  • Clinically similar MCI subjects demonstrate substantial underlying biological heterogeneity.
  • This heterogeneity in biomarkers is critical for understanding individual disease trajectories and predicting conversion to Alzheimer's disease.
Keywords:
ADNIAlzheimer's diseaseAmnestic MCIClusteringHeterogeneity

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